(151b) Strategy to Fit a Downstream Purification Platform for an Early Stage Development, Therapeutic Protein into an Existing Pilot Plant

The development of monoclonal antibodies has gained tremendous interest in the past few years. In terms of bulk manufacturing for early stage clinical studies, speed, product quality and flexibility are the most important drivers. Relatively less emphasis is placed on cost, robustness and capacity during early stages. Pilot plants that are designed to support GMP clinical manufacturing for a portfolio of products, face challenges in supporting the speed and flexibility necessary for early stage development while maximizing efficiencies by leveraging operational platforms across multiple products. The use of operational and equipment platforms at the early development phase can be challenging for a pilot plant facility due to the uncertainty of cell culture product titers, process development unknowns, and clinical supply needs.

This talk will focus on a strategy utilized in a pilot plant to implement a therapeutic protein modular equipment platform that is capable of accommodating a wide range of cell culture titers while minimizing capital expenditure and optimizing the overall operational cost. This proposed approach increased the batch cycle time by approximately 10-15% in order to fit the process requirements to the existing pilot plant equipment. However, the approach also resulted in reduced operational cost by approximately 10-20%. The use of a modular equipment platform has additional long term benefits since downtime between products can be significantly reduced. Timelines required for equipment acquisition, document preparation, SOP development, personnel training and facility preparation/modification can be minimized to approximately 1-2 months at which point, acquiring long lead consumables (filters, resins) or raw materials could be the time limiting factor between programs. The key to defining this modular platform was to understand each unit operation's equipment limitations in order to define a reasonable operational module. In some cases, a single module could accommodate a wide range of input mass; while in other cases a series of modules would be required to process the feed stream. Other elements that the team considered were: (1) ways to reduce equipment utilization by sharing skids between multiple steps and (2) determining the optimum amounts of chromatography resin to minimize operational cost. Implementation of this initiative would have not been possible without active interaction with the development and quality groups to ensure that proposed modifications to the platform would have minimum to no impact to the overall process. This collaborative approach allowed for a rapid implementation and a higher probability of success. This presentation will also include an economic analysis of the proposed platform and the sensitivity of the process economics to several operating variables.